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Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: outcomes from 15 US institutions
- Major, Ajay;
- Yu, Jovian;
- Shukla, Navika;
- Che, Yan;
- Karrison, Theodore G;
- Treitman, Rachel;
- Kamdar, Manali K;
- Haverkos, Bradley M;
- Godfrey, James;
- Babcook, Melissa A;
- Voorhees, Timothy J;
- Carlson, Sophie;
- Gaut, Daria;
- Oliai, Caspian;
- Romancik, Jason T;
- Winter, Allison M;
- Hill, Brian T;
- Bansal, Radhika;
- Bisneto, Jose C Villasboas;
- Nizamuddin, Imran A;
- Karmali, Reem;
- Fitzgerald, Lindsey A;
- Stephens, Deborah M;
- Pophali, Priyanka A;
- Trabolsi, Asaad;
- Schatz, Jonathan H;
- Hu, Marie;
- Bachanova, Veronika;
- Slade, Michael J;
- Singh, Nathan;
- Ahmed, Nausheen;
- McGuirk, Joseph P;
- Bishop, Michael R;
- Riedell, Peter A;
- Kline, Justin
- et al.
Published Web Location
https://doi.org/10.1182/bloodadvances.2023010016Abstract
Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 vs 51 days) and OS (387 vs 131 days) were significantly longer in patients with late (>180 days) vs early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of patients treated with CPI. Most patients (83%) died, commonly because of progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of patients with aggressive B-cell lymphoma treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post-CAR-T outcomes.
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